Biomedical subjects

S X Li

Publications and source records attributed to S X Li.

At least 19 recordsLinked to original sources

PubMed2006

Valsartan treatment reverses erectile dysfunction in diabetic rats.

In order to investigate the effect of angiotensin receptor blockage (ARB) for the treatment on diabetic erectile dysfunction (ED), we used male Sprague-Dawley rats injected with 65 mg/kg streptozotocin to induce diabetes mellitus. The diabetic rats with ED were selected by hypodermic injection of apomorphine (APO) after 8 weeks of model setting. All rats were divided into four groups: G1 (normal control rats), G2 (diabetic rats treated with normal saline), G3 (diabetic rats treated with valsartan) and G4 (diabetic rats treated with spironolactone). After treatment with drugs for 8 weeks, the rate of erection for each group was evaluated after the injection of APO. The intracavernous pressure (ICP) of each rat was then recorded before and after the electrostimulation of the major pelvic ganglion. The rates of erection and the ICP after electrostimulation for diabetic rats treated with valsartan were significantly higher than that in diabetic rats treated with normal saline and spironolactone. The ARB may be an effective therapy for diabetics with ED.

Angiotensin II↗

PubMed2006

Evidence for p-type doping of InN.

The first evidence of successful p-type doping of InN is presented. It is shown that InN:Mg films consist of a p-type bulk region with a thin n-type inversion layer at the surface that prevents electrical contact to the bulk. Capacitance-voltage measurements indicate a net concentration of ionized acceptors below the -type surface. Irradiation with 2 MeV He+ ions is used to convert the bulk of InN:Mg from p to n-type, at which point photoluminescence is recovered. The conversion is well explained by a model assuming two parallel conducting layers (the surface and the bulk) in the films.

Journal Article↗

PubMed2006

A combined DNA vaccine-prime, BCG-boost strategy results in better protection against Mycobacterium bovis challenge.

In this study, we demonstrated that calves vaccinated with a combined DNA vaccine encoding Ag85B, MPT- 64, and MPT-83 antigens from the Mycobacterium tuberculosis for the priming and subsequently boosting with BCG prior to experimental challenge with virulent Mycobacterium bovis (M. bovis) resulted in improved immune responses over immunizing. Vaccination with the combined DNA/BCG induced higher levels of antigen- specific gamma interferon (IFN-gamma) in whole-blood cultures 4 weeks after final vaccination and the level of antigen-specific IFN-gamma in response to Ag85, MPT-64, and MPT-83 were still higher 4 weeks after challenge when compared to the combined DNA group. There was a significant bias toward induction of CD4+ T cells rather than CD8+ T cells responses, and the mean percentage of CD4+ T cells was increased about 2.6-fold in peripheral blood mononuclear cells (PBMC) cultures in DNA prime-BCG boost vaccination when compared to the nonvaccinated group. In addition, DNA prime-BCG boost vaccination resulted in stronger humoral immune responses, and the levels of the specific antibodies to three antigens were increased two- to 32- fold when compared to the combined DNA group. Vaccination with the combined DNA/BCG induced a high level of protection against an intratracheal challenge with virulent M. bovis, based on a significant enhancement of six pathological and microbiological parameters of protection compared to the nonvaccinated group. Finally, the combined DNA/BCG increased the protective efficacy by more than 10-100-fold as measured by reduced CFU counts in the lungs from calves challenged with M. bovis compared to the combined DNA and BCG groups. These results suggest that use of the prime-boost strategy offers better protection against bovine tuberculosis than does the combined DNA vaccines and BCG.

Animals↗

PubMed2005

Combined DNA vaccine encapsulated in microspheres enhanced protection efficacy against Mycobacterium tuberculosis infection of mice.

In a study to develop novel vaccination strategies against tuberculosis, we encapsulated DNA encoding Ag85B, MPT-64 and MPT-83 antigens mixed with dimethyldioctyldecyl ammonium bromide (DDA) into biodegradable poly(dl-lactide-co-glycolide, PLGA) microspheres. Scanning electron microscopy (SEM) analysis demonstrated a uniform microsphere population with a mean diameter of <5microm. Using RT-PCR we were able to demonstrate antigen gene expression in selected tissue. Moreover, in mice injected with PLGA encapsulated DNA, the levels of expression appeared to be higher comparing to those injected with non-encapsulated DNA. Also, C57BL/6 mice immunized with a single dose of PLGA encapsulated DNA produced increased levels of IFN-gamma in the supernatant of spleen cells when cultured in the presence of the recombinant antigens. High levels of specific IgG antibody against the three antigens were also observed. In vaccine/challenge experiments, mice receiving a single dose of PLGA encapsulated DNA were protected against Mycobacterium tuberculosis challenge at levels comparable to groups of mice immunized with three doses of non-encapsulated DNA vaccine or with Mycobacterium bovis BCG.

Adjuvants, Immunologic↗

PubMed2005

Combined DNA vaccines formulated either in DDA or in saline protect cattle from Mycobacterium bovis infection.

We tested the effectiveness of combined DNA vaccines encoding antigens Ag85B, MPT64 and MPT83 from Mycobacterium tuberculosis on cattle. Our results showed that calves treated with combined DNA vaccines in the presence of dimethyldioctyldecyl ammonium bromide (DDA) or saline elicited a strong gamma interferon (IFN-gamma) response 1 or 2 months after the third vaccination. All three antigens induced substantial levels of IFN-gamma production 1 month after the bacterial challenge, when the BCG-driven IFN-gamma levels dropped to less than one third of their peak values. Animals receiving combined DNA vaccines produced highest amounts of IgG antibody titer 2 months after the third vaccination. Steady state low IgG levels were found 2 months after bacterial challenge. A few small lung and lymph node lesions were detected in 1/5 animals treated with combined DNA vaccines, whereas 3/5 of BCG-treated and 5/5 of vector-control calves showed larger and significantly more lesions. About 70- to 100-fold fewer bacteria were found in the lungs and lymph nodes of combined DNA vaccine-treated animals compared to those of the control group. Histopathological analyses showed that vaccinated calves possessed substantially improved post-infection lung and lymph node pathology relative to the controls. Our data indicate that combined DNA vaccines may be used in cattle to combat bovine tuberculosis.

Animals↗

PubMed2002

A new area in the human brain associated with learning and memory: immunohistochemical and functional MRI analysis.

Previous studies identified a new brain area, the marginal division (MrD), at the caudomedial border of the neostriatum in the brain of the rat, cat and monkey. The MrD was distinguishable from the rest of the striatum by the presence of spindle-shaped neurons, specific connections, and dense immunoreactivity for neuropeptides and monoamines in fibers, terminals and neuronal somata. Behavioral testing demonstrated that the MrD contributes to learning and memory in the rat. In the present study, the structure and the function of the MrD were investigated in the human brain. The presence of spindle-shaped neurons and the distribution of neurotransmitters in the MrD were evaluated by immunocytochemical methods. The function of the MrD was identified with functional magnetic resonance imaging (fMRI) of healthy volunteers tested with an auditory digital working memory task. Highly active areas were observed in the prefrontal cortex and MrD with left sided predominance during performance of the task, but other parts of the neostriatum were not excited and the MrD was not activated in a control test of non-working memory. The results of the present investigation therefore indicate the existence of a new area associated with learning and memory function in the human brain. The MrD probably plays an important role in the execution of digital working memory and appears to link the limbic system and the basal nucleus of Meynert. The MrD may also be involved in the mechanism of Alzheimer's disease.

Adult↗

PubMed2002

Pharmacokinetics of ertapenem in healthy young volunteers.

Ertapenem (INVANZ) is a new once-a-day parenteral beta-lactam antimicrobial shown to be effective as a single agent for treatment of various community-acquired and mixed infections. The single- and multiple-dose pharmacokinetics of ertapenem at doses up to 3 g were examined in healthy young men and women volunteers. Plasma and urine samples collected were analyzed using reversed-phase high-performance liquid chromatography with UV detection. Ertapenem is highly bound to plasma protein. The protein binding changes from approximately 95% bound at concentrations of <50 micro g/ml to approximately 92% bound at concentrations of 150 micro g/ml (concentration at the end of a 30-min infusion following the 1-g dose). The nonlinear protein binding of ertapenem resulted in a slightly less than dose proportional increase in the area under the curve from 0 h to infinity (AUC(0- infinity )) of total ertapenem. The single-dose AUC(0- infinity ) of unbound ertapenem was nearly dose proportional over the dose range of 0.5 to 2 g. The mean concentration of ertapenem in plasma ranged from approximately 145 to 175 micro g/ml at the end of a 30-min infusion, from approximately 30 to 34 micro g/ml at 6 h, and from approximately 9 to 11 micro g/ml at 12 h. The mean plasma t(1/2) ranged from 3.8 to 4.4 h. About 45% of the plasma clearance (CL(P)) was via renal clearance. The remainder of the CL(P) was primarily via the formation of the beta-lactam ring-opened metabolite that was excreted in urine. There were no clinically significant differences between the pharmacokinetics of ertapenem in men and women. Ertapenem does not accumulate after multiple once-daily dosing.

Adult↗

PubMed2001

A DNA polymerase beta mutator mutant with reduced nucleotide discrimination and increased protein stability.

DNA polymerase beta (pol beta) offers a simple system to examine the role of polymerase structure in the fidelity of DNA synthesis. In this study, the M282L variant of pol beta (M282Lbeta) was identified using an in vivo genetic screen. Met282, which does not contact the DNA template or the incoming deoxynucleoside triphosphate (dNTP) substrate, is located on alpha-helix N of pol beta. This mutant enzyme demonstrates increased mutagenesis in both in vivo and in vitro assays. M282Lbeta has a 7.5-fold higher mutation frequency than wild-type pol beta; M282Lbeta commits a variety of base substitution and frameshift errors. Transient-state kinetic methods were used to investigate the mechanism of intrinsic mutator activity of M282Lbeta. Results show an 11-fold decrease in dNTP substrate discrimination at the level of ground-state binding. However, during the protein conformational change and/or phosphodiester bond formation, the nucleotide discrimination is improved. X-ray crystallography was utilized to gain insights into the structural basis of the decreased DNA synthesis fidelity. Most of the structural changes are localized to site 282 and the surrounding region in the C-terminal part of the 31-kDa domain. Repositioning of mostly hydrophobic amino acid residues in the core of the C-terminal portion generates a protein with enhanced stability. The combination of structural and equilibrium unfolding data suggests that the mechanism of nucleotide discrimination is possibly affected by the compacting of the hydrophobic core around residue Leu282. Subsequent movement of an adjacent surface residue, Arg283, produces a slight increase in volume of the pocket that may accommodate the incoming correct base pair. The structural changes of M282Lbeta ultimately lead to an overall reduction in polymerase fidelity.

Amino Acid Substitution↗

PubMed2001

Y265H mutator mutant of DNA polymerase beta. Proper teometric alignment is critical for fidelity.

DNA polymerases have the unique ability to select a specific deoxynucleoside triphosphate from a pool of similarly structured substrates. One of these enzymes, DNA polymerase beta, offers a simple system to relate polymerase structure to the fidelity of DNA synthesis. In this study, a mutator DNA polymerase beta, Y265H, was identified using an in vivo genetic screen. Purified Y265H produced errors at a 40-fold higher frequency than the wild-type protein in a forward mutation assay. At 37 degrees C, transient kinetic analysis demonstrated that the alteration caused a 111-fold decrease in the maximum rate of polymerization and a 117-fold loss in fidelity for G misincorporation opposite template A. Our data suggest that the maximum rate of polymerization was reduced, because Y265H was dramatically impaired in its ability to perform nucleotidyl transfer in the presence of the correct nucleotide substrate. In contrast, at 20 degrees C, the mutant protein had a fidelity similar to wild-type enzyme. Both proteins at 20 degrees C demonstrate a rapid change in protein conformation, followed by a slow chemical step. These data suggest that proper geometric alignment of template, 3'-OH of the primer, magnesium ions, dNTP substrates, and the active site residues of DNA polymerase beta are important factors in polymerase fidelity and provide the first evidence that Tyr-265 is important for this alignment to occur properly in DNA polymerase beta.

Bacterial Proteins↗

PubMed2001

Stimulation of pro-alpha(1)(I) collagen by TGF-beta(1) in mesangial cells: role of the p38 MAPK pathway.

Transforming growth factor-beta(1) (TGF-beta(1)) is a potent inducer of extracellular matrix protein synthesis and a key mediator of renal fibrosis. However, the intracellular signaling mechanisms by which TGF-beta(1) stimulates this process remain incompletely understood. In this report, we examined the role of a major stress-activated intracellular signaling cascade, belonging to the mitogen-activated protein kinase (MAPK) superfamily, in mediating TGF-beta(1) responses in rat glomerular mesangial cells, using dominant-negative inhibition of TGF-beta(1) signaling receptors. We first stably transfected rat glomerular mesangial cells with a kinase-deleted mutant TGF-beta type II receptor (TbetaR-II(M)) designed to inhibit TGF-beta(1) signaling in a dominant-negative fashion. Next, expression of TbetaR-II(M) mRNA was confirmed by Northern analysis. Cell surface expression and ligand binding of TbetaR-II(M) protein were demonstrated by affinity cross-linking with (125)I-labeled-TGF-beta(1). TGF-beta(1) rapidly induced p38 MAPK phosphorylation in wild-type and empty vector (pcDNA3)-transfected control mesangial cells. Interestingly, transfection with dominant-negative TbetaR-II(M) failed to block TGF-beta(1)-induced p38 MAPK phosphorylation. Moreover, dominant-negative TbetaR-II(M) failed to block TGF-beta(1)-stimulated pro-alpha(1)(I) collagen mRNA expression and cellular protein synthesis, whereas TGF-beta(1)-induced extracellular signal-regulated kinase (ERK) 1/ERK2 activation and antiproliferative responses were blocked by TbetaR-II(M). In the presence of a specific inhibitor of p38 MAPK, SB-203580, TGF-beta(1) was unable to stimulate pro-alpha(1)(I) collagen mRNA expression in the control and TbetaR-II(M)-transfected mesangial cells. Finally, we confirmed that both p38 MAPK activation and pro-alpha(1)(I) collagen stimulation were TGF-beta(1) effects that were abrogated by dominant-negative inhibition of TGF-beta type I receptor. Thus we show first demonstration of p38 MAPK activation by TGF-beta(1) in mesangial cells, and, given the rapid kinetics, this TGF-beta(1) effect is likely a direct one. Furthermore, our findings suggest that the p38 MAPK pathway functions as a component in the signaling of pro-alpha(1)(I) collagen induction by TGF-beta(1) in mesangial cells.

Animals↗

PubMed2001

Treatment of rotaviral gastroenteritis with Qiwei Baizhu powder.

AIM: To observe the effects of Qiwei Baizhu Powder (QWBZP) on rotaviral gastroenteritis in children and in animal models. METHODS: Enrolled patients were divided into two groups, and one group was treated with oral rehydration solution (ORS) and the other treated with oral liquid of QWBZP. Neonate mice were orally infected with 50 microL rotavirus suspension (4 X 10(8) PFU/mL) and treated with ORS or oral liquid of QWBZP, respectively. RESULTS: Eighty-three cases of rotaviral gastroenteritis treated with QWBZP revealed a better efficacy than that treated with ORS (X(2)=10.87, P < 0.05). The contents of sodium and glucose as well as number of patients with positive human rotavirus antigen in stool in QWBZP group were all less than that in ORS group. In animal models, QWBZP was found effective in treating rotavirus gastroenteritis in neonate NIH mice, as compared with control groups. In QWBZP group, the mortality of infected mice was decreased by 73.3%, the body weight of infected mice was increased, the contents of sodium and glucose as well as number of mice with positive rotavirus antigen in feces were significantly reduced, and the pathological changes such as damage of small intestinal mucosa and villi were also obviously alleviated. CONCLUSION: QWBZP has effects on improving the absorptive function of small intestine, shortening the duration of diarrhea and rotavirus shedding from stool and alleviating the pathological changes of small intestine induced by rotavirus.

Administration, Oral↗

PubMed2001

[Rigid registration and fusion between SPECT and MRI/CT based on external fiducial alignment].

A convenient and effective method of rigid registration and fusion between SPECT and MRI/CT which is based on external fiducial alignment system is designed. After thresholding the image, many image processing arithmetics such as erosion, dilation are used to ensure the corresponding points which will be used to registrate. Then these points are used to minimize the cost function. In this way, an optimal rigid transform is gotten to registrate the images accurately and fuse them well. Error in the registration and fusion is reduced furthest by well designing the N-shape bracket which is used as the external fiducial alignment system and also by limiting the relative displacement between the bracket and the patient. Experimentation shows that this method can realize the registration and fusion of SPECT and MRI/CT effectively.

Algorithms↗

PubMed2000

A new subdivision, marginal division, in the neostriatum of the monkey brain.

A new subdivision, the "marginal division" (MrD), was discovered at the caudal border of the striatum and surrounds the rostral edge of the globus pallidus in the rat brain in our previous studies. The neuronal somata of the MrD are mostly fusiform in shape with their long axes lining dorsoventrally. The MrD is more densely filled with substance P (SP)-, Leucine-enkephalin (L-Enk)-, dynorphin B-, neurotensin-, somatostatin- and cholecystokinin (CCK)-immunoreactive fibers and terminal-like structures than the rest of the striatum. The MrD was confirmed in the cat neostriatum as well. The present study intended to explore whether the MrD exists in the monkey neostriatum (putamen) with Nissl, histochemical and immunohistochemical methods. A band of fusiform neurons were obviously identified at the caudomedial edge of the putamen. These neurons lie outside the lateral medullary lamina and indirectly surround the rostrolateral border of the globus pallidus. The abundance of SP-, L-Enk-, neuropeptide Y-, CCK-, dopamine- and serotonin-positive fibers and terminal-like structures with a few positive fusiform neurons accumulating at the caudomedial border of the putamen obviously distinguishes this zone from the rest of neostriatum and globus pallidus. The acetylcholinesterase (AChE) positive and nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) containing fusiform neurons are distinctly visualized in the same zone. The morphological figure and the location of these neurons, and the histochemical and immunohistochemical characteristics of this area coincide well with those of the MrD in the rat and cat striatum. This study thus convincingly identifies the existence of the MrD in the monkey neostriatum. It is fairly asserted that the MrD is a universal structure in the mammalian brain.

Animals↗

PubMed2000

[Analysis on contents of flavonoids and polysaccharides in pollen of Typha angustifolia L. and its different processed products].

OBJECTIVE: To explore the relationship between processing of the pollen of Typha angustifolia (TA) and the fluctuation of contents of its effective components--flavonoids and polysaccharides. METHOD: The contents of flavonoids and polysaccharides in TA and in the different processed products of TA were determined by spectrophotometry. RESULTS: The contents of flavonoids in TA changed as follows: unprocessed TA(1) > TA stir fried with yellow wine(2) > TA stir fried with vinegar(3) > TA dried at 140 degrees C (4) > parched TA(5) > TA dried at 180 degrees C (6) > scorched TA(7) > TA dried at 220 degrees C (8) > charcoal TA(9). The statistic analysis showed that the flavonoid contents in raw TA were significantly different from those in the different processed products (P < 0.01) of TA except 2. The polysaccharide contents increased in 4, 5, 6 and 7 significantly (P < 0.01 or P < 0.05), while decreased in 9 significantly (P < 0.01). As compared with the polysaccharide contents in 1, no significant changes occurred in those in 2 and 8. CONCLUSION: Processing temperature, yellow wine and vinegar could stimulate the content change of chemical constituents in TA, influencing flavonoids and polysaccharides in different degrees.

Flavonoids↗

PubMed2000

[Determination of dimethyldiphenylurea in dibase-propellant by gas chromatography].

By using gas chromatography external standard method, dimethyldiphenylurea in the storage propellant was separated and determined. Being compared with the conventional bromination method, this one is more rapid, precise and reproducible. Moreover, it can provide reliable data for evaluationg the quality grade of the propellant.

English Abstract↗

PubMed2000

[A 3D brachytherapy treatment planning system].

Brachytherapy dose prescription and treatment playing lag behind the state-of-the-art for external beam therapy. We have developed a computer program on a SGI Indigo2 graphics workstation to plan the loading or stereotactic implantation of radioactive seeds. The treatment planning system, using data from the pre-treatment diagnostic CT scan or MRI scan, contours target areas on sequential images creating a 3-dimensional target volume, and is based on a dose algorithm of TG-43 formalism. The treatment isodose contour is generated at each scanningplane, reconstructed sagittal and coronal views, and overlaid on the corresponding target contour for 3-dimensional coverage visualization. Volume dose histograms are generated for the target and neighboring normal structures. We also provide two orthogonal digitally reconstructed projected images identifying virtual source positions superimposed on for fluoroscopy guided loading applicators and sources.

Algorithms↗

PubMed2000

[The development of a brain surgery path planning system].

Based on the patient's CT/MRI Section images, the brain surgery path Planning system makes surgeon freely draw out the interesting regions through the use of feasible interactive drawing contour function. And by fast judgement, the system is able to give out the risky value of the path. Finally, the system would directly show the surgery path in 3-D display.

Brain↗

PubMed1999

Involvement of phenylalanine 272 of DNA polymerase beta in discriminating between correct and incorrect deoxynucleoside triphosphates.

DNA polymerase beta is a small monomeric polymerase that participates in base excision repair and meiosis [Sobol, R., et al. (1996) Nature 379, 183-186; Plug, A., et al. (1997) Proc. Natl. Acad. Sci. U.S.A. 94, 1327-1331]. A DNA polymerase beta mutator mutant, F272L, was identified by an in vivo genetic screen [Washington, S., et al. (1997) Proc. Natl. Acad. Sci. U.S.A. 94, 1321-1326]. Residue 272 is located within the deoxynucleoside triphosphate (dNTP) binding pocket of DNA polymerase beta according to the known DNA polymerase beta crystal structures [Pelletier, H., et al. (1994) Science 264, 1891-1893; Sawaya, M., et al. (1997) Biochemistry 36, 11205-11215]. The F272L mutant produces errors at a frequency 10-fold higher than that of wild type in vivo and in the in vitro HSV-tk gap-filling assay. F272L shows an increase in the frequency of both base substitution mutations and frameshift mutations. Single-enzyme turnover studies of misincorporation by wild type and F272L DNA polymerase beta demonstrate that there is a 4-fold decrease in fidelity of the mutant as compared to that of the wild type enzyme for a G:A mismatch. The decreased fidelity is due primarily to decreased discrimination between the correct and incorrect dNTP during ground-state binding. These results suggest that the phenylalanine 272 residue is critical for maintaining fidelity during the binding of the dNTP.

Base Pair Mismatch↗